This is a proposal for a competing renewal of an Independent Scientist Award. The first four years of his award have allowed the PI to develop new lines of research, make substantial contributions to the discipline, and expand his research skills considerably. The PI proposes to continue these activities, now adding ligand binding assays and the use of viral vectors and other ways to modify gene expression in the brain to his array of skills. These are very powerful tools to analyze the molecular and cellular basis of behavior. The PI proposes to use these tools to study the functional significance of sex differences in vasopressin innervation of the brain. The central hypothesis driving this grant is that sex differences in neurotransmitter systems may induce sex differences in brain functions and behaviors as well as prevent them. The latter would occur to compensate for hormonal and physiological sex differences that might otherwise have caused undesirable sex differences. Parental behavior in rodents such as prairie voles, in which males as well as females care for the young, is a good example. Hormonal changes associated with pregnancy prime the brain of females for parental behavior. By necessity males must use a different strategy to be parental. This grant explores to what extent the sexually dimorphic vasopressin projections of the bed nucleus of the stria terminalis and amygdala help male and female voles to generate qualitatively similar parental behavior. These projections, which stimulate parental behavior in males, are much denser in males than in females. The plan is to study how vasopressin or its antagonists influence parental behavior at different stages of the reproductive cycle. The prediction is that interference with vasopressin transmission should cause sex differences in behaviors that otherwise are similar. A second aim is to study whether sex differences in these responses are caused by sex differences in gonadal hormone levels during development. A third aim is to study whether social conditions that minimize sex differences in parental behavior also change the involvement of vasopressin in parental behavior. Finally, experiments are planned to determine where in the brain vasopressin is likely to control parental behavior in a sexually dimorphic manner. Experiments will test whether social conditions that influence parental behavior change vasopressin receptor occupancy differently in males and females and whether changes in vasopressin receptor expression in turn influence parental behavior. By virtue of its theme, this project will increase what little knowledge is available on the neural control of paternal behavior as well as on the role of sex differences in the brain. Also, by showing that the effects of neuropeptides on behaviors are state- and sex-dependent, this study may affect drug therapies that are based on manipulating neurotransmission, because it underscores the notion that these therapies should be developed independently for men and women.